Previous studies indicate that elevated levels of plasma homocyst(e)ine are strongly associated with the occurrence of occlusive vascular diseases. To explore whether elevated plasma homocyst(e)ine concentrations are the causative agent of cardiovascular diseases, we generated mice that have moderately and severely elevated homocyst(e)ine concentrations. These mice represent a model for severe homocyst(e)inemia, which results from the complete lack of cystathionine a-synthase. Of these mice, the heterozygous mutants were determined to be promising models for studying the in vivo role of elevated levels of homocyst(e)ine in the etiology of cardiovascular diseases.